This PhD position is integral to the TOP-GUT MSCA DN project (details: https://cordis.europa.eu/project/id/101119911 and https://topgut.eu/). This project recruits 11 PhD students and we are looking for you as our new motivated and dedicated PhD student. Your research focusses on the development of a 3D gut chip aimed at overcoming the constraints of current in vitro gut models. The project's central objective is to faithfully replicate the physiological attributes of the intestinal lumen using biofabrication methods, including the incorporation of a patterned collagen scaffold to emulate the architectural characteristics of human intestinal villi within a microfluidic device. This '3D gut chip' is envisioned to deliver a 3D tissue structure exposed to fluidic shear, thereby enhancing cell differentiation and physiological function, with a particular emphasis on ameliorating absorptive permeability and biotransformation processes.

Your primary objectives:

• develop hydrogel constructs capable of accurately replicating the crypt-villus features of the intestinal lumen;
• cultivate intestinal organoids on the patterned hydrogels and rigorously assess their functional maturation, considering spatial cell arrangement and mucus production, among other factors;
• integrate the developed topographical elements into a perfusable microfluidic device with both apical and basal access points;
• investigate the barrier and biotransformation activities of various molecules, encompassing those of bacterial origin, dietary components, and pharmaceutical compounds, under both static and dynamic (flow) conditions within the '3D gut chip.'

To achieve these objectives, advanced techniques in 3D cell culturing and biofabrication will be employed. Furthermore, state-of-the-art methodologies will be applied to functionally characterise intestinal cells, including analytical techniques and spatial imaging. Additionally, microfluidic systems and flow modeling will be harnessed to elucidate the biological handling and transformation of drugs and nutrients in the context of health and disease. It is noteworthy that within the TOP-GUT project, the inclusion of stromal compartments and immune cells will expand the scope of investigation.

• a Bachelor's or Master's degree in a relevant field such as Bioengineering, Biotechnology, Biomedical Sciences, or a related discipline;
• a strong background in cell culture, tissue engineering, and microfluidics;
• experience with 3D cell culture and biofabrication techniques (highly desirable);
• proficiency in experimental design, data analysis, and problem-solving;
• excellent communication skills and the ability to work both independently and as part of a collaborative team;
• demonstrated passion for translational research and an eagerness to contribute to the advancement of in vitro gut models.

• a position for 4 years a full time PhD position for 4 years (the first three years are funded by the Marie Curie Doctoral Networks programme of the European Commission, the fourth year by Utrecht University);
• a full-time gross salary starting from €2,770 in the first year and increasing to €3,539 in the fourth year in scale P;
• 8% holiday bonus and 8.3% end-of-year bonus;
• a pension scheme, partially paid parental leave, and flexible employment conditions based on the Collective Labour Agreement Dutch Universities.

In addition to the employment conditions from the CAO for Dutch Universities, Utrecht University has a number of its own arrangements. These include agreements on professional development, leave arrangements, sports and cultural schemes and you get discounts on software and other IT products. We also give you the opportunity to expand your terms of employment through the Employment Conditions Selection Model. This is how we encourage you to grow.

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Silvia Mihăilă's research group is part of the Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University. Her group specialises in developing advanced in vitro models that seamlessly combine biofabrication techniques and organoid cultures. The primary goal is to advance our comprehension of health and disease by harnessing microenvironmental cues, particularly through the manipulation of topographical and geometrical parameters, to fine-tune and optimise cellular processes, which can be pharmaceutically targeted. This multidisciplinary approach holds the promise of deepening our insights into the intricate mechanisms underlying health and disease.

Yvonne Vercoulen’s research group is part of the Center for Molecular Medicine, University Medical Center Utrecht. Dr. Vercoulen’s team investigates how cellular interactions and inflammatory signaling promote tissue disease, such as inflammation and cancer. We develop advanced imaging technology in primary tissues and make use of culture systems (oganoids) that mimic the human gut. The team fosters collaborations with expert clinicians in gastroenterology through research meetings for optimal exchange of knowledge, promoting clinical impact.